PMID- 36508695
OWN - NLM
STAT- MEDLINE
DCOM- 20221214
LR  - 20221222
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 41
DP  - 2022 Jan-Dec
TI  - Dapansutrile ameliorated chondrocyte inflammation and osteoarthritis through 
      suppression of MAPK signaling pathway.
PG  - 9603271221145401
LID - 10.1177/09603271221145401 [doi]
AB  - INTRODUCTION: Osteoarthritis (OA) is one of the most common joint diseases in the 
      elderly population. Proinflammatory cytokines, such as Interleukin-1beta (IL-1beta), 
      play an important role in the development and progression of OA. Dapansutrile is 
      a specific inhibitor of the NOD-like receptor protein 3 (NLRP3) inflammasome and 
      exhibits anti-inflammatory properties. METHODS: In this study, we investigated 
      the protective effect and the underlying mechanism of dapansutrile on cartilage 
      degeneration in vitro and in vivo. In the present study, chondrocytes were 
      isolated from rats and then were treated with dapansutrile. After that, the 
      expression of (Cox-2, inducible nitric oxide synthase (iNOS), Mmp-3, Mmp-9, 
      Mmp-13 and IL-10) were evaluated at RNA level, then the expression of (COX-2, 
      MMP-3, MMP-9, MMP-13, SOX-9 and COL2) were evaluated at protein level. 
      Subsequently, the activation of the mitogen-activated protein kinase (MAPK) 
      pathway was tested using western blotting (WB). Additionally, the rat OA model 
      was developed to evaluate the protective effects of dapansutrile in vivo. 
      RESULTS: The results showed that dapansutrile had no obvious cytotoxicity on rat 
      chondrocytes at 24 h (0, 1, 2, 5 and 10 muM). Dapansutrile significantly decreased 
      IL-1beta-induced upregulation of COX2, iNOS, matrix metalloproteinase 3 (MMP3), 9 
      (MMP9) and 13 (MMP13), and reversed IL-1beta-induced the downregulation of IL-10, 
      SOX9 and COL2. Dapansutrile also inhibited IL-1beta-induced upregulation of the MAPK 
      signaling pathway by downregulating the expression levels of phospho-ERK, and 
      phospho-P38 in a concentration dependent manner. In addition, dapansutrile 
      exhibited protective effects in rat OA model with lower Mankin's score and 
      Osteoarthritis Research Society International (OARSI) score. CONCLUSION: Our 
      study suggested that dapansutrile effectively inhibited chondrocyte inflammation 
      by suppressing MAPK signaling pathway in vitro, and ameliorated cartilage 
      degeneration in vivo, indicating an anti-inflammatory effect in OA treatment.
FAU - Tang, L
AU  - Tang L
AUID- ORCID: 0000-0003-4255-9921
AD  - Department of Emergency Medicine, 89681The Second Affiliated Hospital Zhejiang 
      University School of Medicine, Hangzhou City, Zhejiang, China.
FAU - Sim, I
AU  - Sim I
AD  - Department of Oncology, Clinical Institute, 89681Pyongyang Medical University, 
      Pyongyang, Democratic People's Republic of Korea.
AD  - Department of Orthopedic Surgery, 89681The Second Affiliated Hospital Zhejiang 
      University School of Medicine, Hangzhou City, Zhejiang Province, China.
FAU - Moqbel, Saa
AU  - Moqbel S
AD  - Department of Emergency Medicine, 89681The Second Affiliated Hospital Zhejiang 
      University School of Medicine, Hangzhou City, Zhejiang, China.
FAU - Wu, L
AU  - Wu L
AUID- ORCID: 0000-0002-2561-6069
AD  - Department of Orthopedic Surgery, 89681The Second Affiliated Hospital Zhejiang 
      University School of Medicine, Hangzhou City, Zhejiang Province, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - 0 (NF-kappa B)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Anti-Inflammatory Agents)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Aged
MH  - Rats
MH  - Humans
MH  - Animals
MH  - Matrix Metalloproteinase 13/genetics/metabolism
MH  - *Matrix Metalloproteinase 3/metabolism/pharmacology/therapeutic use
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Interleukin-10
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Chondrocytes
MH  - *Osteoarthritis/genetics
MH  - Interleukin-1beta/metabolism
MH  - Inflammation/metabolism
MH  - Signal Transduction
MH  - Anti-Inflammatory Agents/pharmacology/therapeutic use
MH  - Cyclooxygenase 2/metabolism
OTO - NOTNLM
OT  - Interleukin-1beta
OT  - Osteoarthritis
OT  - dapansutrile
OT  - matrix metalloproteinase
OT  - mitogen-activated protein kinase pathway
EDAT- 2022/12/13 06:00
MHDA- 2022/12/15 06:00
CRDT- 2022/12/12 15:53
PHST- 2022/12/12 15:53 [entrez]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
AID - 10.1177/09603271221145401 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221145401. doi: 
      10.1177/09603271221145401.